Chemical libraries such as those provided by the present invention are useful per se and are appreciated to be valuable in and of themselves. Indeed, such libraries can be sold or leased in unaltered form. Moreover, such libraries generally possess biological activity themselves, e.g. antibacterial effect, or can be screened to provide useful compounds such as lead or ultimate drugs, pesticides, industrial chemical species and other useful materials.
The area of combinatorial chemistry has burgeoned recently to the point where it has begun to influence the course of drug discovery (Service, R. F., Science, 1996, 272, 1266-1268). Most of the combinatorial organic synthesis to date has involved the use of solid phase methods with a very few instances of solution phase chemistry reported. Cheng, S., et al., J. Am. Chem. Soc., 1996, 118, 2567-73. In most cases, solid-phase, parallel synthesis is applied to provide pooled mixtures or discrete compounds in volumes which accommodate high-throughput bioassays. Thus far, there has been scant interest in “one-pot”, essentially simultaneous functionalization of multiple sites. Ostresh, J. M., et al., J. Biopolymers, 1994, 34, 1681-1689; Carell, T., et al., Chem. Biol. 1995, 2, 171-83; and Shipps, G. W. Jr., et al., Bioorg. Med. Chem., 1996, 4, 655-657.
There would be great benefit attained from the provision of combinatorial libraries which can be formed in solution phase, especially in essentially single reaction vessel reactions. Similar benefit would attend solution phase synthesis of such libraries under conditions which ensure representation in the product library of all possible reaction products formable under the reaction condition extant from the reactants selected for use. A further benefit would attend the preparation of such libraries from scaffold or backbone molecules possessing a relatively large number of derivatizable reaction sites. The present invention provides for the achievement of the foregoing goals.